In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 3 ( 2022-3-9), p. e3001578-
Abstract:
Neurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, the exact role of protein aggregation in the pathophysiology of these disorders remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of protein aggregation, and the investigation of early dynamic events associated with inclusion formation. Here, we report on the development of a light-inducible protein aggregation (LIPA) system that enables spatiotemporal control of α-synuclein (α-syn) aggregation into insoluble deposits called Lewy bodies (LBs), the pathological hallmark of Parkinson disease (PD) and other proteinopathies. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical, and ultrastructural features of authentic LBs observed in PD-diseased brains. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration and PD-like motor impairments. Collectively, our findings provide a new tool for the generation, visualization, and dissection of the role of α-syn aggregation in PD.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001578
DOI:
10.1371/journal.pbio.3001578.g001
DOI:
10.1371/journal.pbio.3001578.g002
DOI:
10.1371/journal.pbio.3001578.g003
DOI:
10.1371/journal.pbio.3001578.g004
DOI:
10.1371/journal.pbio.3001578.g005
DOI:
10.1371/journal.pbio.3001578.t001
DOI:
10.1371/journal.pbio.3001578.s001
DOI:
10.1371/journal.pbio.3001578.s002
DOI:
10.1371/journal.pbio.3001578.s003
DOI:
10.1371/journal.pbio.3001578.s004
DOI:
10.1371/journal.pbio.3001578.s005
DOI:
10.1371/journal.pbio.3001578.s006
DOI:
10.1371/journal.pbio.3001578.s007
DOI:
10.1371/journal.pbio.3001578.s008
DOI:
10.1371/journal.pbio.3001578.s009
DOI:
10.1371/journal.pbio.3001578.s010
DOI:
10.1371/journal.pbio.3001578.s011
DOI:
10.1371/journal.pbio.3001578.s012
DOI:
10.1371/journal.pbio.3001578.s013
DOI:
10.1371/journal.pbio.3001578.s014
DOI:
10.1371/journal.pbio.3001578.s015
DOI:
10.1371/journal.pbio.3001578.s016
DOI:
10.1371/journal.pbio.3001578.s017
DOI:
10.1371/journal.pbio.3001578.s018
DOI:
10.1371/journal.pbio.3001578.s019
DOI:
10.1371/journal.pbio.3001578.r001
DOI:
10.1371/journal.pbio.3001578.r002
DOI:
10.1371/journal.pbio.3001578.r003
DOI:
10.1371/journal.pbio.3001578.r004
DOI:
10.1371/journal.pbio.3001578.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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